Alcohol alkoxylate containing materials have been used in a wide variety of industrial applications, for example as nonionic surfactants, additives, and conjugates for biologically-active molecules. They are typically prepared by the reaction of an alcohol with an alkylene epoxide such as ethylene oxide (i.e. oxirane) or propylene oxide (i.e. 2-methyoxirane) in the presence of one or more catalysts.
Known catalyst systems and processes for the alkoxylation of alcohols include Lewis acids such as boron trifluoride or silicon tetrafluoride, alone in combination with metal hydrides, fluorides, alkyls or alkoxides. Such acidic materials also catalyze side reactions such as dimerization of alkylene epoxides to form highly undesirable dioxanes during the alkylalkoxylation. For this reason many processes use strongly basic catalysts to alkoxylate alcohols. However, some alcohols are not stable to strong base. For instance, halohydrins, XCR2CR2OH (X=halogen), are well known to form epoxides in the presence of base and are used for this purpose synthetically to convert olefins to epoxides.
Alcohol alkoxylates wherein the alcohol group bears a reactive functional group are of interest in several applications. They are useful for the synthesis of new molecules and materials bearing one or more alkoxylate chains such as novel surfactants and metal ligating agents. As another example, the binding of polyethylene glycol (PEG) to biological molecules (peptides, proteins), known as “PEGylation”, is used to modify the physical and solution properties of those molecules to enhance their pharmaceutical properties.
Alkoxylates useful for these synthetic reactions are substituted with a functionalized alcohol group at only one end of the alkoxylate chain. However, known methods for the preparation of such mono-alkoxylates involve multistep procedures and require tedious separations. A one-step alkoxylation of an appropriately substituted alcohol would present a significant advance. However, the functional groups commonly used to bind PEGs to other molecules undergo ready reaction with base, especially the strong alkoxide bases required to catalytically alkoxylate alcohols. For a one-step process to be successful the functional group must be unreactive towards the alkoxylation catalyst.
There exists a need therefore for catalysts suitable for the selective alkoxylation of functionalized alcohols